Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression

Jiani Yin; Chun-An Chun; Nikolay N Zavadenko; Natalia L Pechatnikova; Oxana Yu Naumova; Harsha V Doddapaneni; Jianhong Hu; Donna M Muzny; Christian P Schaaf; Elena L Grigorenko

doi:10.3390/genes11080853

Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression

Genes (Basel). 2020 Jul 25;11(8):853. doi: 10.3390/genes11080853.

Authors

Jiani Yin^{1

2

3}, Chun-An Chun^{1

2}, Nikolay N Zavadenko⁴, Natalia L Pechatnikova⁴, Oxana Yu Naumova^{5

6

7}, Harsha V Doddapaneni⁸, Jianhong Hu⁸, Donna M Muzny⁸, Christian P Schaaf^{1

2

9}, Elena L Grigorenko^{1

6

7}

Affiliations

¹ Molecular and Human Genetics Department, Baylor College of Medicine, Houston, TX 77030, USA.
² Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
³ Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
⁴ Neurology, Neurosurgery and Medical Genetics, Department of Pediatrics, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
⁵ Texas Institute for Measurement, Evaluation, and Statistics, University of Houston, Houston, TX 77024, USA.
⁶ Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia.
⁷ Laboratory of Translational Developmental Sciences, Saint Petersburg State University, 199034 Saint Petersburg, Russia.
⁸ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
⁹ Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany.

Abstract

Approximately 30% of individuals with autism spectrum disorder (ASD) experience developmental regression, the etiology of which remains largely unknown. We performed a complete literature search and identified 47 genes that had been implicated in such cases. We sequenced these genes in a preselected cohort of 134 individuals with regressive autism. In total, 16 variants in 12 genes with evidence supportive of pathogenicity were identified. They were classified as variants of uncertain significance based on ACMG standards and guidelines. Among these were recurring variants in GRIN2A and PLXNB2, variants in genes that were linked to syndromic forms of ASD (GRIN2A, MECP2, CDKL5, SCN1A,PCDH19, UBE3A, and SLC9A6), and variants in the form of oligogenic heterozygosity (EHMT1, SLC9A6, and MFSD8).

Keywords: ACMG standards and guidelines; autism; developmental regression; exon capture and sequencing; variant classification.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autism Spectrum Disorder / genetics*
Autism Spectrum Disorder / pathology*
Child
Child, Preschool
Cohort Studies
Disease Progression
Female
Gene Expression Regulation*
Genetic Markers*
Genetic Predisposition to Disease*
High-Throughput Nucleotide Sequencing / methods*
Humans
Infant
Male
Mutation*

Substances

Genetic Markers

Grants and funding

UM1HG008898/NH/NIH HHS/United States